Abstract

In the future, entire genomes tailored to specific functions and environments could be designed using computational tools. However, computational tools for genome design are currently scarce. Here we present algorithms that enable the use of design-simulate-test cycles for genome design, using genome minimisation as a proof-of-concept. Minimal genomes are ideal for this purpose as they have a very simple functional assay, the cell can either replicate or not. We used the first (and currently only published) whole-cell model, for the bacterium Mycoplasma genitalium. Our computational design-simulate-test cycles discovered novel in-silico minimal genomes smaller than JCVI-Syn3.0, a bacterial cell with the currently known smallest genome that can be grown in pure culture. In the process, we identified 10 low essentiality genes, 18 high essentiality genes, and produced evidence for at least two minimal genomes for Mycoplasma genitalium in-silico. This work brings combined computational and laboratory genome design and construction a step closer.

Footnotes

Revisions to title and changes in phrasing and tone to the arguments presented in the paper. One genome design algorithm was revised, implemented computationally, renamed, and produced new results. Numbers throughout the paper have been updated to reflect new results. Only two of the original figures remain, the others are replaced with three new figures, and the table is updated. A Supplementary Information is now provided, as is a completed Methods section. Computational details have been fleshed out throughout the paper.

Copyright

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.